Escherichia coli strains bearing plasmids containing genes coding for colicin V have been isolated frequently from bacteremias and other deep infections of humans and some lower animals. Genes on colicin V plasmids (pColV) are now known to code for some determinants which probably facilitate such bacterial invasiveness. Among the determinents is the capacity to adhere to the epithelial surfaces of the mouse small intestine. In the research proposed, recombinant DNA technology, biochemical methods and experiments with germfree and gnotobiotic mice will be used in a study of the mechanisms by which E. coli pColV strains adhere to intestinal micosae. Colicin V plasmids from several sources will be characterized as to molecular weight and restriction enzyme pattern. Restriction fragments of the DNA of one of the plasmids will be cloned into E. coli plasmid vectors. E. coli strains containing such cloned sequences will be screened with antibody specific for determinants coded by the colicin V plasmids. Surface macromolecules detected in such a fashion will be characterized biochemically and tested for their capacity to adhere to intestinal epithelial cells. The molecules and specific antibody to them also will be tested for their capacity to inhibit or enhance specific adhesion of E. coli pColV cells to intestinal cells. Adhesive macromolecules and antibodies to them will be used as well as specific ligands in efforts to identify the receptor for the bacterial adhesives in the intestinal epithelial cells. In addition, a comprehensive study will be undertaken of the mechanisms of pathogenesis of E. coli pColV strains in which various properties coded by genes on the plasmids will be assessed for their function in the virulence of the bacteria in a mouse model.